Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion
Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion
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DOI：
10.1038/ni1374
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发表时间：
2006-09-01
影响因子：
30.5
通讯作者：
Kinashi, Tatsuo
中科院分区：
文献类型：
--
作者：
Katagiri, Koko;Imamura, Masashi;Kinashi, Tatsuo
RAPL是一种结合小GT受体Rap 1的蛋白质，是有效的免疫细胞运输所必需的。在这里，我们已经确定了激酶Mst 1作为RAPL的关键效应子。RAPL调节Mst 1的定位和激酶活性。编码Mst 1的基因的“敲低”证明了其诱导极化形态和整合素LFA-1聚集以及由趋化因子和T细胞受体连接触发的粘附的需要。RAPL和Mst 1定位于囊泡隔室，并在Rap 1激活后与LFA-1动态易位至前缘，表明RAPL-Mst 1复合物在LFA-1的细胞内转运中具有调节功能。我们的研究证明了一个以前未知的功能Mst 1中继Rap 1-RAPL信号诱导细胞极性和粘附的淋巴细胞。
RAPL, a protein that binds the small GTPase Rap1, is required for efficient immune cell trafficking. Here we have identified the kinase Mst1 as a critical effector of RAPL. RAPL regulated the localization and kinase activity of Mst1. 'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the induction of both a polarized morphology and integrin LFA-1 clustering and adhesion triggered by chemokines and T cell receptor ligation. RAPL and Mst1 localized to vesicular compartments and dynamically translocated with LFA-1 to the leading edge upon Rap1 activation, suggesting a regulatory function for the RAPL-Mst1 complex in intracellular transport of LFA-1. Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes.